CHEMOTHERAPY RESPONSIVENESS OF HUMAN-TUMORS AS 1ST TRANSPLANT GENERATION XENOGRAFTS IN THE NORMAL MOUSE - 6-DAY SUBRENAL CAPSULE ASSAY

CHEMOTHERAPY RESPONSIVENESS OF HUMAN-TUMORS AS 1ST TRANSPLANT GENERATION XENOGRAFTS IN THE NORMAL MOUSE - 6-DAY SUBRENAL CAPSULE ASSAY
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DOI:
10.1002/1097-0142(19810701)48:1
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发表时间:
1981-01-01
期刊:
影响因子:
6.2
通讯作者:
ESBER, HJ
ESBER, HJ
中科院分区:
医学1区
文献类型:
--
作者:
BOGDEN, AE;COBB, WR;ESBER, HJ

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通过在6天时间范围内将肾包膜下(SRC)测定方法应用于新鲜手术外植体,证明了在正常免疫活性小鼠中利用人肿瘤作为第1代移植物异种移植物用于确定肿瘤对化疗剂的敏感性的可行性。在将254个异种移植物植入对照动物的试验中,对总共37个人乳腺肿瘤进行了测试。在6天试验期内,50(20%)个对照品显示出一定程度的部分消退。使用肿瘤大小出现正变化的平均对照生长作为可评价性标准,第1代移植人乳腺肿瘤的可评价测定率为86%。通过对32种先前未经治疗的乳腺癌测试8种临床活性药物[甲氨蝶呤、己烯雌酚、L-苯丙氨酸氮芥、丙酸睾酮、5-氟尿嘧啶、环磷酰胺、阿霉素、他莫昔芬],获得了肿瘤反应谱。获得的反应模式表明,没有单一的药物对所有肿瘤都有活性,对一种药物有反应的肿瘤也不一定对另一种药物有反应,这表明预测个体肿瘤对特定化疗药物的反应是可行的。如果这8种药物是活性未知的开发药物,并首次针对此类人类肿瘤进行测试,则结果不仅可以预测其临床活性,而且肿瘤缓解率还可以指示每种药物用于乳腺癌特异性治疗的相对潜力。
Feasibility of utilizing human tumors as 1st transplant generation xenografts in the normal immunocompetent mouse for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay methodology to fresh surgical explants in a 6-day time frame. A total of 37 human breast tumors were tested in assays in which 254 xenografts were implanted into control animals. Fifty (20%) of the controls showed some degree of partial regression in the 6-day assay period. Using a mean control growth having a positive change in tumor size as the criterion for evaluability, 1st transplant generation human breast tumors provided an evaluable assay rate of 86%. A tumor response profile was obtained as a result of testing 8 clinically active drugs [methotrexate, diethylstilbestrol, L-phenylalanine mustard, testosterone proprionate, 5-fluorouracil, cytoxan, adriamycin, tamoxifen] against 32 previously untreated breast cancers. The pattern of responses obtained indicated that no single agent was active against all tumors, nor were tumors which were responsive to 1 agent necessarily responsive to another, suggesting the feasibility of predicting individual tumor response to specific chemotherapeutic agents. Had these 8 drugs been developmental agents of unknown activity which were being tested for the 1st time against such a panel of human tumors the results would have not only predicted their clinical activity, but the tumor response rates would have also provided an indication of the relative potential of each drug for the specific treatment of breast cancer.